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Crystal structure of a human CD3-ε/δ dimer in complex with a UCHT1 single-chain antibody fragment

2004; National Academy of Sciences; Volume: 101; Issue: 46 Linguagem: Inglês

10.1073/pnas.0407359101

1091-6490

Kelly L. Arnett, Stephen C. Harrison, Don C. Wiley,

CAR-T cell therapy research

The α/β T cell receptor complex transmits signals from MHC/peptide antigens through a set of constitutively associated signaling molecules, including CD3-ε/γ and CD3-ε/δ. We report the crystal structure at 1.9-Å resolution of a complex between a human CD3-ε/δ ectodomain heterodimer and a single-chain fragment of the UCHT1 antibody. CD3-ε/δ and CD3-ε/γ share a conserved interface between the Ig-fold ectodomains, with parallel packing of the two G strands. CD3-δ has a more electronegative surface and a more compact Ig fold than CD3-γ; thus, the two CD3 heterodimers have distinctly different molecular surfaces. The UCHT1 antibody binds near an acidic region of CD3-ε opposite the dimer interface, occluding this region from direct interaction with the TCR. This immunodominant epitope may be a uniquely accessible surface in the TCR/CD3 complex, because there is overlap between the binding site of the UCHT1 and OKT3 antibodies. Determination of the CD3-ε/δ structure completes the set of TCR/CD3 globular ectodomains and contributes information about exposed CD3 surfaces.